Photothermal therapy (PTT) employing near-infrared (NIR)-absorbing nanoparticles to generate heat from optical energy to kill cancer cells has gained great attention in recent years [1-4]. Most photothermal conducting agents are based on various gold (Au) nanostructures, including nanoshells [5, 6], nanorods [7, 8], and nanocages [9, 10]. In addition, the multifunctional probes with both therapeutic functions and imaging capabilities (e.g., magnetic resonance imaging) were also developed with traditional designs focusing on building Au nanoshell around magnetic nanoparticle core [11-15]. While various dual functional nanomaterials have been employed for PTT, virtually all those composed of iron oxide were nanocomposites also requiring a material that is thermally responsive to NIR light (usually gold) [11-15].
Despite the overwhelming potential of nanoparticle-mediated PTT to improve cancer treatment, lack of clinical approval restricts availability to a very narrow subset of cancer patients. The only nanoparticle-mediated PTT that has advanced to clinical trials is Aurolase therapy, consisting of Au nanoshells with a silica core, which was first investigated in patients with head and neck tumors and more recently for primary and metastatic lung tumors. However, the ˜150 nm gold nanoshells are larger than the ideal size range to maximize exploitation of the enhanced permeability and retention (EPR) effect [5]. Although they are relatively biocompatible, they are not biodegradable and are too large to be excreted renally [16]; consequently, their long term effects are not well understood. Au nanorods, Au nanocages and Au nanoshells with iron oxide cores also face many of the same challenges as silica-core Au nanoshells [12]. Furthermore, nanorods lack photostability due to a “melting” phenomenon resulting from point and planar defects caused by application of laser light [17]. Clinical application of other non-biodegradable PTT mediators such as carbon nanotubes is also limited by potential long-term toxicity [18, 19].
Highly crystallized iron oxide nanoparticles (HCIONPs) made from thermal decomposition have been reported years ago by different groups with the ability to control the size from 5-40 nm [20-24, herein incorporated by reference in their entireties and specifically for describing HCIONPs]. These nanoparticles have been widely used as magnetic resonance imaging (MRI) contrast agents and imagine guidable drug carriers as well as inducers of magnetic hyperthermia under an alternating magnetic field [25-28]. Although magnetic iron oxide nanocrystals offer the ideal characteristics of clinically suitable nanoparticles and can meet all the criterion desired for PTT mediators, few works have been reported using magnetic nanoparticles only for effective PTT probably due to their low photothermal efficiency [29]. Last year researchers in Taiwan produced surface-modified IONPs (˜440 nm) via a hydrothermal reaction that enhanced optical absorption in the NIR range, and it was postulated that this effect could be attributed to ligand-Fe complexes on the Fe3O4 nanoparticle surfaces [30].